A Combination of Ulinastatin and Xuebijing Amplifies Neuroprotection after Transient Cerebral Ischemia via Attenuating Apoptosis Signal Pathways in Hippocampus

Background: Ulinastatin (UTI) plays the beneficial roles in modifying cerebral ischemic injury evoked by cardiac arrest (CA). XueBiJing (XBJ), comprised of extracts from Chinese herbals, has been used for the treatment of sepsis and ischemic disorders linked to multiple organ dysfunction syndromes. The current study was to find interventions that can enhance effectiveness of these drugs and further to provide a fundamental for their rational application in clinical practice. Thus, we examined how apoptosis signal in the hippocampus is engaged in a facilitating role of UTI and XBJ in improving neural injury and neurological functions after transient cerebral ischemia. Methods: CA was induced by asphyxia followed by cardiopulmonary resuscitation in rats. Western Blot analysis and ELISA were employed to determine the protein expression of Caspase-3 and Caspase-9 in the hippocampus; and representative apoptosis pathways. The modified neurological severity score (mNSS) and spatial working memory performance were used to assess neurological deficiencies in CA rats. Results: CA increased Caspase-3 and Caspase-9 in the hippocampus CA1 region. A lower dose of UTI did not attenuate upregulation of apoptosis signal pathways evoked by CA. However, a systemic administration of XBJ significantly amplified the inhibitory effects of the lower dose of UTI on apoptosis signal of the hippocampus. In addition, a combination of UTI and XBJ improved mNSS and spatial working memory performance to a greater degree. Conclusions: Our data indicate that a combination of XBJ and UTI plays a facilitating role in improving neuronal injury and neurological deficits observed in transient cerebral ischemia; and an inhibition of apoptosis signal pathways is involved in neuroprotective effects of united XBJ and UTI.